ObjectiveTo summarize the mechanism of endoplasmic reticulum stress (ERS) in liver diseases. MethodWe sorted out and summarized the studies related to ERS and liver diseases in recent years. ResultsEndoplasmic reticulum plays important roles in protein folding, calcium ion storage, and lipid synthesis in cells. Endoplasmic reticulum stress will be induced when the number of misfolded/unfolded proteins in the endoplasmic reticulum increases or the calcium ion homeostasis is unbalanced. The endoplasmic reticulum regulates the unfolded protein response through three transmembrane receptor proteins to initiate corresponding pathways for restoring endoplasmic reticulum homeostasis. Prolonged stress can lead to metabolic disorders. Mild ERS can promote the progression of hepatocellular carcinoma, and continuous ERS will induce cell apoptosis and plays an anti-tumor effect; ERS can promote lipid accumulation in non-alcoholic fatty liver disease and aggravate the progression of the disease; in hepatic ischemia reperfusion injury, ERS activation will aggravate liver damage. Meanwhile, ERS activation plays an important pathogenic role in the pathogenesis of drug-induced liver injury. ConclusionERS plays a crucial regulatory role in the occurrence and development of liver-related diseases, providing a theoretical basis and new approach for targeted ERS therapy in liver diseases.